Lead toxicity is a serious environmental and societal problem affecting intelligence, behavior and health. Lead toxicity is defined by the U.S. Center for Disease Control in terms of the lead concentration in blood: a lead content in blood above 25 micrograms per deciliter of whole blood, associated with an erythrocyte proptoporphyrin concentration of at least 35 micrograms per deciliter, is considered toxic. A test for lead in blood, however, reflects only the exposure during the few months prior to the test and may not reflect the whole-body burden. Accordingly, when the blood test indicates lead poisoning, a further test is performed before treatment to determine the skeletal lead burden. These time-consuming and burdensome tests require the analysis of the urine following the administering of a chelating agent that causes lead to be removed from fluids and bone.
An alternative diagnostic approach involves measuring the skeletal lead concentration in vivo by x-ray fluorescence (XRF). XRF-based in vivo analysis for lead began in the mid-1970's with the pioneering work at the University of Lund in Sweden. The development and relative merits of the principal techniques employed for XRF-based skeletal lead measurement are discussed in the review article by Todd and Chettle entitled “In Vivo X-Ray Fluorescence of Lead in Bone: Review and Current Issues” (Environment Health Perspectives, vol. 102, no. 2 (February 1994)), the contents of which are incorporated herein by reference. The standard technique adopted by research laboratories throughout the world for the in vivo study of lead in bone uses the 88 keV gamma ray emitted by the radioactive source Cd109 to fluoresce the K x-rays of lead. State-of-the-art instruments employing this technique have detection limits of a few parts per million, allowing researchers to explore potential toxicities in wide groups of the population.
While offering excellent sensitivity, accuracy and precision, the standard technique has significant problems associated therewith. Utilization of a radioisotope source has inherent disadvantages: it cannot be turned off, requires licensing and periodic replacement, and poses onerous problems with disposal. Furthermore, testing conducted by the standard K x-ray technique requires about thirty minutes (during which the subject must be immobilized) to gather sufficient counts for statistically significant measures of the lead concentration. That long duration, with its concomitant costs, precludes the test being used for routine clinical evaluations.
The disadvantages of the standard K x-ray technique have prompted exploration of the potential of measuring the lead concentration using the L x-rays of lead, fluoresced responsive to irradiation by relatively low-power x-rays that can be generated by x-ray tubes. The Lα and Lβ x-rays, at 10.5 keV and 12.6 keV respectively, have little penetrating power so that the measurements are typically restricted to bones, such as the tibia and patella, with minimal overlying tissue, and only the first quarter-millimeter of the bone is investigated. In an early example of this approach disclosed by Rosen et al. in U.S. Pat. No. 4,845,729, screening for lead toxicity is performed by irradiating a test subject's tibia with x-rays produced by a silver-anode x-ray tube, and acquiring a spectrum of the fluoresced radiation and comparing the Lα and Lβ x-ray peaks to the corresponding peaks in spectra obtained from patients diagnosed (by the conventional blood testing) with lead toxicity.
As is extensively discussed by Todd et al. in “L-Shell X-Ray Fluorescence Measurements of Lead in Bone: Accuracy and Precision” (Phys. Med Biol., vol. 47, pp. 1399-1419 (2002)), a significant limitation on the accuracy and precision of lead concentration measurements based on detection of L x-rays arises from the sensitivity of such measurements on the thickness of tissue overlying the irradiated bone. While various direct and indirect techniques are currently available (e.g., ultrasound gauges) for determination of overlying tissue thickness, such techniques may yield results having relatively large inherent variability, thereby compromising the accuracy and precision of lead concentration measurements that rely on determination of tissue thickness. Moreover, the overlying tissue is not homogeneous but instead consists of both skin and adipose tissue (subcutaneous fat), which attenuate the L x-rays differently, so that both thicknesses must be known in the conventional methods of analysis if the concentrations are to be measured accurately.
In U.S. Pat. No. 5,461,654, the contents of which are incorporated herein by reference, Grodzins et al. propose an XRF-based method for determination of the concentration of lead and bone from the intensities of the Lα and Lβ x-rays that is purportedly insensitive to the thickness and composition of the tissue overlying the irradiated bone. It is believed by the present inventor, however, that this proposed method, which is based upon a thin-layer approximation of the lead-containing bone, may not produce reliable results for bones of clinical interest, i.e., bone having a thickness in excess of 1 mm and thus being “infinitely” thick for the L x-rays of lead.